Selective Oxidation of Disparate Functional Groups Mediated by a Common Aspartic Acid-Based Peptide Catalyst Platform.

As drug molecules become increasingly complex, the need to develop new or improved strategies for the efficient and selective synthesis and editing of bioactive compounds grows. Inspired by the high selectivity and fast rates exhibited in many enzymatic reactions to assemble complex natural products, our group and others have developed peptide-based catalysts to mediate synthetically relevant transformations that can be orthogonal, or akin to, native enzymatic reactivity. Peptide catalysts offer several useful features, such as modularity, ease of synthesis, and often enhanced compatibility with synthetic reaction conditions.In one intriguing area, our group has employed the proteinogenic amino acid aspartic acid (Asp) as a catalytic residue embedded within short peptide sequences to selectively introduce a singular oxygen atom into increasingly complex scaffolds, which might constitute a type of single atom editing. Our strategy has involved the development of an aspartic acid/peracid catalytic shuttle, a mechanism that, to our knowledge, has not yet been documented in enzymes.Our foray into Asp-catalyzed oxidation began with the discovery of a peptide sequence to impart enantioselectivity in the epoxidation of minimal olefins. This platform was then extended to include nucleophilic Baeyer-Villiger oxidations and electrophilic